This invention is generally in the area of biological reactors and in particular is a method and apparatus for selective removal of chemical species from a biological fluid.
The removal of chemical species from the bloodstream using extracorporeal devices offers several advantages over conventional treatment modalities, such as transfusion therapy or the injection of a drug antagonist. In some instances, extracorporeal reactors may be the only therapy practical for toxins for which no antagonist is available.
Unfortunately, the complexity of the blood presents a number of problems. Mechanical damage to the cells can cause a low hematocrit or activation of the immune system. Damage to platelets can cause bleeding, a stroke or other clotting disorder. The high viscosity of blood and packing of the cells makes conventional filtration difficult due to blockage and nonspecific reactions or binding.
Extracorporeal reactors containing immobilized species have been constructed using three different types of solid phase configurations: particles, hollow fibers and planar sheets. Of these, particles provide the highest surface area per unit volume. The large surface area can potentially bind large quantities of various species which specifically react with the substances to be removed or treated in the blood.
At the present time, utilization of particles or "beads" for extracorporeal reactors is limited by packing of the solid phase in the device. This restricts the flow rates through the device to approximately 25 ml/min or less. Treatment of the entire blood volume of an adult patient, approximately 5,000 ml, through contact with the immobilized species within the device would require an impossible amount of time due to the risk and discomfort to the patient.
In order to use an extracorporeal reactor with particles or "beads" at clinically useful blood flow rates, a method of maintaining these beads in a suspended state is required. The desired flow rates are in the range of between approximately 50 ml/min to an excess of 1,000 ml/min. A second factor is that the device must be aprrovable by the Food and Drug Administration. All of the materials from which the unit is fabricated, as well as the unit as a whole, must be tested extensively before the device can be considered safe. Other considerations include a minimal priming volume, preferably not exceeding 300 ml, a means for preventing the "beads" from passing into the patient's bloodstream, and relatively easy assembly, cleaning, operation and modification, as required for the individual patient.
There are other applications of such a device for processing of biological solutions containing cellular materials or having a high viscosity. An example would be the removal of specific proteins expressed in a procaryotic expression system where conventional filtration causes cell death and release of degrading enzymes.
It is therefore an object of the present invention to provide a reactor chamber providing maximum surface area for reaction with a biological fluid, particularly cellular suspensions, such as blood or cell culture suspensions.
It is a further object of the present invention to provide a means to suspend and retain particles within the reactor chamber.
It is still a further object of the present invention to provide a reactor chamber having useful flow rates of from approximately 50 ml/min to an excess of 1,000 ml/min and a priming volume of less than approximately 300 ml.
It is another object of the present invention to provide a reactor chamber which is non-toxic, relatively easy to assemble and operate, and can meet FDA requirements.